ESTRO 2024 - Abstract Book

S5163

Radiobiology - Immuno-radiobiology

ESTRO 2024

Rats (Fischer 344) were cranially irradiated with a single high dose of protontherapy (15 Gy or 25 Gy) using FLASH dose rate proton irradiation (257 ± 2 Gy/s) or conventional dose rate proton irradiation (4 ± 0.02 Gy/s) and the toxicities in the normal tissue were examined by histological, cytometric and behavioral analysis. Glioblastoma bearing rats were irradiated in the same manner and tumor-infiltrating leukocytes were quantified by flow cytometry.

Results:

Our findings indicate that supplemental oxygen has an adverse impact on both functional and anatomical evaluations of normal brain following conventional and FLASH proton therapy. In addition, oxygen supplementation in anesthesia is particularly detrimental for anti-tumor immune response by preventing a strong immune cell infiltration into tumoral tissues following conventional proton therapy.

Conclusion:

These results demonstrate the need to further optimize anesthesia protocols used in radiotherapy to preserve normal tissues and achieve tumor control, specifically when combination with immunotherapy drugs is foreseen.

Keywords: Protontherapy, FLASH, oxygen

1170

Digital Poster

Improving checkpoint inhibition therapy in solid tumors by combining with other cancer treatments

Priyanshu M Sinha 1 , Folefac Charlemagne Asonganyi 1 , Pernille B Elming 1 , Mateusz K Sitraz 2 , Michael R Horsman 1

1 Aarhus University Hospital, Department of Experimental Clinical Oncology - Department of Oncology, Aarhus, Denmark. 2 Aarhus University Hospital, Danish Center of Particle Therapy, Aarhus, Denmark

Purpose/Objective:

Introduction: There is a great focus on establishing combinational therapies in clinics where radiotherapy or chemotherapy is often given along with immunotherapy, in order to improve the overall clinical outcome. This would then make the tumors more immunogenic, as dying tumor cells release antigens that would then stimulate the immune cells. These immune cells when activated would identify and kill tumors in a immune mediated cell death mechanisms [1]. This is the principle of the cancer immune cycle, and holds great importance for solid tumors, as majority of them are traditionally known to be poor candidates for checkpoint inhibition therapy. Our plan would be to investigate the combination of one such inhibitor (anti-CTLA-4; anti-cytotoxic T lymphocyte associated protein - 4) with treatments that have shown to have both direct and indirect cell killing mechanisms. These includes (i) high dose proton radiation, (ii) the vascular disrupting agent (VDA) OXi4503, and (iii) hyperthermia; where all of these treatments not only have the potential to kill tumor cells, but also have shown to mediate tumor immunogenicity